Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTJMI34A)

• DOT Name: Cornifin-A (SPRR1A)
• Synonyms: 19 kDa pancornulin; SPRK; Small proline-rich protein IA; SPR-IA
• Gene Name: SPRR1A
• Related Disease:
  B-cell lymphoma
  Head and neck carcinoma
  Lung cancer
  Papillomatosis
  Squamous cell carcinoma
  Esophageal squamous cell carcinoma
  Atopic dermatitis
  Breast cancer
  Cutaneous squamous cell carcinoma
• UniProt ID: SPR1A_HUMAN
• Pfam ID: PF02389
• Sequence:
  MNSQQQKQPCTPPPQPQQQQVKQPCQPPPQEPCIPKTKEPCHPKVPEPCHPKVPEPCQPK
  VPEPCQPKVPEPCPSTVTPAPAQQKTKQK
• Function: Cross-linked envelope protein of keratinocytes. It is a keratinocyte protein that first appears in the cell cytosol, but ultimately becomes cross-linked to membrane proteins by transglutaminase. All that results in the formation of an insoluble envelope beneath the plasma membrane.
• Reactome Pathway: Formation of the cornified envelope (R-HSA-6809371)

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
B-cell lymphoma	DISIH1YQ	Strong	Altered Expression	[1]
Head and neck carcinoma	DISOU1DS	Strong	Altered Expression	[2]
Lung cancer	DISCM4YA	Strong	Biomarker	[3]
Papillomatosis	DISV4NMP	Strong	Biomarker	[4]
Squamous cell carcinoma	DISQVIFL	Strong	Biomarker	[4]
Esophageal squamous cell carcinoma	DIS5N2GV	moderate	Altered Expression	[5]
Atopic dermatitis	DISTCP41	Limited	Altered Expression	[6]
Breast cancer	DIS7DPX1	Limited	Altered Expression	[5]
Cutaneous squamous cell carcinoma	DIS3LXUG	Limited	Altered Expression	[5]

6 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Cornifin-A (SPRR1A).	[7]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Cornifin-A (SPRR1A).	[8]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Cornifin-A (SPRR1A).	[9]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil increases the expression of Cornifin-A (SPRR1A).	[10]
Permethrin	DMZ0Q1G	Approved	Permethrin increases the expression of Cornifin-A (SPRR1A).	[11]
phorbol 12-myristate 13-acetate	DMJWD62	Phase 2	phorbol 12-myristate 13-acetate increases the expression of Cornifin-A (SPRR1A).	[12]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Cornifin-A (SPRR1A).	[13]

References

• [1] Clinical implications of SPRR1A expression in diffuse large B-cell lymphomas: a prospective, observational study.BMC Cancer. 2014 May 14;14:333. doi: 10.1186/1471-2407-14-333.
• [2] The combined use of EFS, GPX2, and SPRR1A expression could distinguish favorable from poor clinical outcome among epithelial-like head and neck carcinoma subtypes.Head Neck. 2019 Jun;41(6):1830-1845. doi: 10.1002/hed.25623. Epub 2019 Jan 16.
• [3] Identification of cancer biomarkers of prognostic value using specific gene regulatory networks (GRN): a novel role of RAD51AP1 for ovarian and lung cancers.Carcinogenesis. 2018 Mar 8;39(3):407-417. doi: 10.1093/carcin/bgx122.
• [4] Localization and expression of cornifin-alpha/SPRR1 in mouse epidermis, anagen hair follicles, and skin neoplasms.J Invest Dermatol. 1996 Apr;106(4):647-54. doi: 10.1111/1523-1747.ep12345463.
• [5] Clinical significance of SPRR1A expression in progesterone receptor-positive breast cancer.Tumour Biol. 2015 Apr;36(4):2601-5. doi: 10.1007/s13277-014-2879-8. Epub 2014 Nov 26.
• [6] Expression of Cornified Envelope Proteins in Skin and Its Relationship with Atopic Dermatitis Phenotype.Acta Derm Venereol. 2017 Jan 4;97(1):36-41. doi: 10.2340/00015555-2482.
• [7] Retinoic acid and hydroquinone induce inverse expression patterns on cornified envelope-associated proteins: implication in skin irritation. J Dermatol Sci. 2014 Nov;76(2):112-9. doi: 10.1016/j.jdermsci.2014.08.003. Epub 2014 Aug 26.
• [8] Long-term estrogen exposure promotes carcinogen bioactivation, induces persistent changes in gene expression, and enhances the tumorigenicity of MCF-7 human breast cancer cells. Toxicol Appl Pharmacol. 2009 Nov 1;240(3):355-66.
• [9] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [10] Multi-level gene expression profiles affected by thymidylate synthase and 5-fluorouracil in colon cancer. BMC Genomics. 2006 Apr 3;7:68. doi: 10.1186/1471-2164-7-68.
• [11] Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
• [12] Keratinocyte differentiation marker suppression by arsenic: mediation by AP1 response elements and antagonism by tetradecanoylphorbol acetate. Toxicol Appl Pharmacol. 2001 Aug 1;174(3):302-11.
• [13] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.